The diagnostic accuracy of intraoperative frozen section biopsy for diagnosis of sentinel lymph node metastasis in breast cancer patients: a meta-analysis

: Sentinel lymph node (SLN) sampling is important for evaluating the nodal stage of breast cancer when the axillary nodes are clinically free of metastasis. The intraoperative frozen section (IFS) of SLN is used for lymph node assessment. This meta-analysis aims to provide evidence about the diagnostic accuracy and the applicability of IFS of SLN in breast cancer patients. Data were collected by searching PubMed, Cochrane, Scopus, and Web of Science electronic databases for trials matching our eligibility criteria. The statistical analysis included the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and pooled studies' diagnostic odds ratio outcomes. The analyses were conducted using the Open Meta-analyst software. This meta-analysis pooled the results of 110 studies. The overall sensitivity of IFS for SLN metastasis was 74.7%; 95% CI [72.0, 77.2], P < 0.001. It was 31.4% 95% CI [25.2, 38.3], P < 0.001 for the micro-metastasis, and 90.2%; 95% CI [86.5, 93.0], P < 0.001 for the macro-metastasis. The overall specificity was 99.4%; 95% CI [99.2, 99.6], P < 0.001. The overall positive likelihood ratio was 121.4; 95% CI [87.9, 167.6], P < 0.001, and the overall negative likelihood ratio was 0.226; 95% CI [0.186, 0.274], P < 0.001. The overall diagnostic odds ratio of IFS for diagnosing SLN metastasis was 569.5; 95% CI [404.2, 802.4], P < 0.001. The intraoperative frozen section of SLN has good sensitivity for diagnosing breast cancer macro-metastasis. However, the sensitivity is low for micro-metastasis. The specificity is very satisfactory

Cardioprotection à la phase aiguë de l'infarctus

Prompt reperfusion remains the mainstay strategy for reducing myocardial infarct size and improving outcomes. Paradoxically, reperfusion itself may induce myocardial damage termed, reperfusion injury. Improvements in morbidity and mortality would not be achieved by reperfusion without new adjunctive therapies. Although ischemic postconditionning (IPost, brief intermittent periods of ischemia and reflow applied at the onset of reperfusion following sustained ischemia) has been successful in attenuating infarct size in all species including humans, its use is limited to patients with ongoing acute myocardial infarction subjected to coronary angioplasty. IPost has been shown to exert its cardioprotective effect by upregulating prosurvival kinases named RISK (consisting of PI3K/Akt and ERK1/2) and the downstream target GSK-3β. 1) First, we thought to compare the cardioprotective effect of IPost and a pharmacological cardioprotective agent (erythropoietin, EPO), known to activate the same signalling pathways. In our model, EPO showed a trend for better protective effects than IPost through higher phosphorylation levels of ERK1/2 and GSK-3β. 2) Second, we examined whether EPO-induced cardioprotection is maintained in presence of type I diabetes and insulin resistance syndrome. Diabetic rat hearts were refractory to EPO-induced cardioprotection with altered components of RISK signalling pathway that inhibit GSK-3β. Moreover, this lack of cardioprotection was not dose-related, since higher EPO doses did not restore the cardioprotective effects. Interestingly, direct inhibition of GSK-3β may provide an alternative therapeutic option to reduce infarct size in presence of diabetes. On the other hand, the cardioprotective effect of EPO was maintained in our model of insulin resistance syndrome. 3) In the third part of this work we thought to examine the mechanism involved in remote postconditionning (RIPost)-induced cardioprotection. RIPost, a non-invasive application of brief ischemia in remote organs just before myocardial reperfusion, is a novel approach to attenuate reperfusion injury. In our model, RIPost was as effective as local IPost to prevent reperfusion injury with trend superiority to RIPost. Similarly to IPost, RIPost activated RISK pathway. GSK-3β would be implicated in RIPost-induced cardioprotection.La reperfusion coronaire précoce et complète est le moyen le plus efficace pour limiter l'étendue de l'infarctus myocardique. Revers de la médaille, cette reperfusion est à l'origine des lésions nommées lésions de reperfusion. La recherche d'un moyen protecteur qui limite la survenue de ces lésions a un intérêt clinique majeur. Le postconditionnement ischémique (IPost) qui désigne l'application de plusieurs séquences d'ischémie/reperfusion au moment de la reperfusion coronaire peut prévenir la survenue des lésions de reperfusion mais il n'est applicable qu'aux patients reperfusés par angioplastie. Le mécanisme d'action du IPost passe en partie par l'activation de la voie RISK (composée de la voie PI3K/Akt et ERK1/2) et le sous-effecteur en commun la GSK-3β. 1) Dans la première partie du travail nous avons comparé l'effet cardioprotecteur d'un agent pharmacologique activateur de la voie RISK (l'érythropoïétine ; EPO) à celui du IPost dans un même modèle expérimental. Une meilleure cardioprotection a été observée avec l'EPO, résultante d'une meilleure phosphorylation d'ERK1/2 et de la GSK-3β. 2) Après avoir apprécié la cardioprotection induite par EPO chez des rats sains, nous avons testé son effet chez des rats ayant un diabète type I ou une insulino-résistance. Une inhibition de l'effet cardioprotecteur de l'EPO a été observée chez les rats diabétiques avec une altération de la voie RISK et par conséquence une absence de la phosphorylation de la GSK-3β. Par contre, son effet a été maintenu en présence d'une insulino-résistance. Une dose plus élevée d'EPO n'a pas restauré la cardioprotection. Alors que l'effet protecteur de l'EPO est altéré en présence du diabète, les inhibiteurs de la GSK-3β semble être une alternative efficace, puisque l'injection de SB216763 (un inhibiteur de la GSK-3β) a induit un effet protecteur dans notre modèle de rat diabétique. 3) Dans la troisième partie du travail nous nous sommes attachés à mieux comprendre le mécanisme cardioprotecteur du postconditionnement à distance (RIPost). Cette application non invasive de brefs séquences d'ischémie/reperfusion au niveau d'un organe à distance du coeur permet d'atténuer les lésions de reperfusion myocardique. L'effet cardioprotecteur du RIPost a été comparable à celui d'un IPost local avec une activation des mêmes voies de signalisation (RISK/GSK-3β)

Cardioprotection à la phase aiguë de l'infarctus

La reperfusion coronaire précoce et complète est le moyen le plus efficace pour limiter l'étendue de l'infarctus myocardique. Revers de la médaille, cette reperfusion est à l'origine des lésions nommées lésions de reperfusion. La recherche d'un moyen protecteur qui limite la survenue de ces lésions a un intérêt clinique majeur. Le postconditionnement ischémique (IPost) qui désigne l'application de plusieurs séquences d'ischémie/reperfusion au moment de la reperfusion coronaire peut prévenir la survenue des lésions de reperfusion mais il n'est applicable qu'aux patients reperfusés par angioplastie. Le mécanisme d'action du IPost passe en partie par l'activation de la voie RISK (composée de la voie PI3K/Akt et ERK1/2) et le sous-effecteur en commun la GSK-3b. 1) Dans la première partie du travail nous avons comparé l'effet cardioprotecteur d'un agent pharmacologique activateur de la voie RISK (l'érythropoïétine ; EPO) à celui du IPost dans un même modèle expérimental. Une meilleure cardioprotection a été observée avec l'EPO, résultante d'une meilleure phosphorylation d'ERK1/2 et de la GSK-3b. 2) Après avoir apprécié la cardioprotection induite par EPO chez des rats sains, nous avons testé son effet chez des rats ayant un diabète type I ou une insulino-résistance. Une inhibition de l'effet cardioprotecteur de l'EPO a été observée chez les rats diabétiques avec une altération de la voie RISK et par conséquence une absence de la phosphorylation de la GSK-3b. Par contre, son effet a été maintenu en présence d'une insulino-résistance. Une dose plus élevée d'EPO n'a pas restauré la cardioprotection. Alors que l'effet protecteur de l'EPO est altéré en présence du diabète, les inhibiteurs de la GSK-3b semble être une alternative efficace, puisque l'injection de SB216763 (un inhibiteur de la GSK-3b) a induit un effet protecteur dans notre modèle de rat diabétique. 3) Dans la troisième partie du travail nous nous sommes attachés à mieux comprendre le mécanisme cardioprotecteur du postconditionnement à distance (RIPost). Cette application non invasive de brefs séquences d'ischémie/reperfusion au niveau d'un organe à distance du coeur permet d'atténuer les lésions de reperfusion myocardique. L'effet cardioprotecteur du RIPost a été comparable à celui d'un IPost local avec une activation des mêmes voies de signalisation (RISK/GSK-3b).Prompt reperfusion remains the mainstay strategy for reducing myocardial infarct size and improving outcomes. Paradoxically, reperfusion itself may induce myocardial damage termed, reperfusion injury. Improvements in morbidity and mortality would not be achieved by reperfusion without new adjunctive therapies. Although ischemic postconditionning (IPost, brief intermittent periods of ischemia and reflow applied at the onset of reperfusion following sustained ischemia) has been successful in attenuating infarct size in all species including humans, its use is limited to patients with ongoing acute myocardial infarction subjected to coronary angioplasty. IPost has been shown to exert its cardioprotective effect by upregulating prosurvival kinases named RISK (consisting of PI3K/Akt and ERK1/2) and the downstream target GSK-3b. 1) First, we thought to compare the cardioprotective effect of IPost and a pharmacological cardioprotective agent (erythropoietin, EPO), known to activate the same signalling pathways. In our model, EPO showed a trend for better protective effects than IPost through higher phosphorylation levels of ERK1/2 and GSK-3b. 2) Second, we examined whether EPO-induced cardioprotection is maintained in presence of type I diabetes and insulin resistance syndrome. Diabetic rat hearts were refractory to EPO-induced cardioprotection with altered components of RISK signalling pathway that inhibit GSK-3b. Moreover, this lack of cardioprotection was not dose-related, since higher EPO doses did not restore the cardioprotective effects. Interestingly, direct inhibition of GSK-3b may provide an alternative therapeutic option to reduce infarct size in presence of diabetes. On the other hand, the cardioprotective effect of EPO was maintained in our model of insulin resistance syndrome. 3) In the third part of this work we thought to examine the mechanism involved in remote postconditionning (RIPost)-induced cardioprotection. RIPost, a non-invasive application of brief ischemia in remote organs just before myocardial reperfusion, is a novel approach to attenuate reperfusion injury. In our model, RIPost was as effective as local IPost to prevent reperfusion injury with trend superiority to RIPost. Similarly to IPost, RIPost activated RISK pathway. GSK-3b would be implicated in RIPost-induced cardioprotection.ANGERS-Bib. électronique (490079901) / SudocSudocFranceF

Barbaloin Protects Pentylenetetrazol-Induced Cognitive Deficits in Rodents via Modulation of Neurotransmitters and Inhibition of Oxidative-Free-Radicals-Led Inflammation

Background: Epilepsy is defined by an excessive level of activity in the neurons and coordinated bursts of electrical activity, resulting in the occurrence of seizure episodes. The precise cause of epileptogenesis remains uncertain; nevertheless, the etiology of epilepsy may involve neuroinflammation, oxidative stress, and malfunction of the neurotransmitter system. Objective: The goal of this investigation was to assess barbaloin’s protective properties with respect to pentylenetetrazol (PTZ)-)-induced cognitive deficits in rats via antioxidative, anti-inflammatory, and neurotransmitter-modulating effects. Methods: Wistar rats were subjected to PTZ [40 mg/kg (i.p.)], which induced cognitive decline. Behavior assessment using a kindling score, open-field test (OFT), novel object recognition test (NORT), and assays for superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA), acetylcholinesterase (AChE), caspase-3, nitric oxide (NO), interleukins-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, nuclear factor kappa-B (NF-κB), Bcl-2 and Bax, and neurotransmitter levels [GABA, DA, NE, and serotonin (5-HT)] were performed. Results: The treatment of rats with barbaloin resulted in behavior improvement and significant changes in the levels of GSH, SOD, CAT, MDA, AChE, NO, IL-6, IL-1β, TNF-α, NF-κB, caspase-3, Bcl-2, and Bax compared to the PTZ control group. Barbaloin treatment resulted in notable changes in neurotransmitter levels (GABA, NE, 5-HT, DA) compared to the PTZ group. Conclusions: The ongoing study has gathered evidence indicating that the injection of barbaloin has resulted in significant improvements in cognitive performance in rats. This is achieved by inhibiting oxidative stress, enhancing the activity of natural antioxidant enzymes, reducing cytokine levels, and increasing the levels of neurotransmitters in the brain. These results were detected in comparison to a PTZ control and can be attributed to the potent anti-inflammatory and antioxidant capabilities of barbaloin, which could be linked to its neuroprotective properties. Barbaloin may potentially increase cognitive decline and boost neuronal survival by altering the expression of Bax, caspase-3, Bcl-2.</i

Oxyphenbutazone ameliorates carfilzomib induced cardiotoxicity in rats via inhibition of oxidative free radical burst and NF-κB/IκB-α pathway

Carfilzomib (CFZ), a chemotherapeutic agent used for multiple myeloma treatments reported to cause high incidence of cardiac events either new onset and/or exacerbate formerly diagnosed heart failure with ventricular and myocardial dysfunction.Purpose: Current research designed to explore and examine the preventive effect of oxyphenbutazone in the CFZ -instigated cardiotoxicity. Methodology: Female Wistar Rats weighing 200–250 g selected randomly and grouped as follows: Group 1 designated as the Normal control and receive normal saline only. Group 2 served toxic control and exposed to CFZ (4 mg/kg, intraperitoneally [i.p.]). Group 3 &amp; 4 served as treatment groups and administered with CFZ concomitantly orally fed with oxyphenbutazone at doses of 35 and 70 mg/kg/three times a week, respectively. The total duration of experimental protocol was of 21 days. After completion of the experiments animals subjected to blood collection using light ether anesthesia and serum was separated for biochemical analysis further. The serum levels of Mg+2, Ca+2 and cardiac enzymes (aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB) levels were estimated. Later animals sacrificed and heart tissue isolated for further examinations. Intracellular proteins NFkB and IkBα were estimated by western blot. Results: The serum analysis revealed that CFZ administration significantly elevated the levels of LDH, CK and CKMB in CFZ exposed animals when compared to normal animals while administration of oxyphenbutazone significantly reduced these biochemical changes, Intracellular antioxidant enzymes and NF-kB in treatment groups as compared to disease control animals. Conclusion: Findings of the research protocol suggests significant injuries to cardiac tissues when animals exposed to CFZ and Oxyphenbutazone protected the cardiac tissues